This invention relates to solid formulations of the 43-dimethylphosphinate ester of rapamycin (AP23573):

In in vitro and in vivo xenograft models, AP23573 has potently inhibited proliferation of a variety of human tumor cell lines, including prostate, endometrial, soft tissue and bone sarcoma, leukemia, lymphoma and glioblastoma cell lines.
Human clinical studies with AP23573 have yielded promising results in patients with various cancers, including possible delay in the time to progression or recurrence of tumors.
AP23573 is also in studies aimed at the development of AP23573-eluting stents. The role of AP23573 in that context is to inhibit restenosis following introduction of the stent.
Based in part on the known biological activities for other mTOR inhibitors, AP23573 may also be useful for a range of indications susceptible to treatment with an mTOR inhibitor, including without limitation, the treatment and prevention of organ transplant rejection and autoimmune diseases, fungal infection, multiple sclerosis; rheumatoid arthritis, systemic lupus erythematosus [see e.g., U.S. Pat. No. 5,078,999], pulmonary inflammation [U.S. Pat. No. 5,080,899], insulin dependent diabetes mellitus [U.S. Pat. No. 5,321,009], skin disorders, such as psoriasis [U.S. Pat. No. 5,286,730], bowel disorders [U.S. Pat. No. 5,286,731], smooth muscle cell proliferation and intimal thickening following vascular injury [U.S. Pat. Nos. 5,288,711 and 5,516,781], adult T-cell leukemia/lymphoma [European Patent Application 525,960 A1], ocular inflammation [U.S. Pat. No. 5,387,589], malignant carcinomas [U.S. Pat. No. 5,206,018], cardiac inflammatory disease [U.S. Pat. No. 5,496,832], and anemia [U.S. Pat. No. 5,561,138].
One important challenge for the development and use of AP23573 is the development of storage stable solid dosage forms suitable for oral administration. More specifically, we have found that AP23573 tablets prepared by direct compression of non-micronized AP23573 with standard excipients and fillers, in the presence or absence of antioxidants, has thus far provided suboptimal tablets which did not exhibit desirably high homogeneity or stability.